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Diagnosis of CAA during Life

Neuroimaging of CAA

  • Chapter
Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders

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Abstract

Intensive efforts are underway to develop diagnostic tests, which enable us to detect cerebral amyloid angiopathy (CAA) at an early preclinical stage. These tests should be noninvasive to allow for broad and repeated application. Specific neuroimaging methods targeted at the hallmark constituent of CAA, the Aβ deposits, are particularly attractive goals. A useful technique has to be significantly more sensitive and specific than the currently available structural and functional imaging modalities. One of the main problems is the limited distribution and accumulation in brain of amyloid specific probes, such as radiolabeled Aβ-peptides or anti-Aβ monoclonal antibodies even after invasive modes of administration, e.g., intracisternal injection. Looking at a systemic approach, the impermeability of the blood-brain barrier for amyloid probes requires the incorporation of an efficient delivery strategy. In pursuit of this, animal studies have demonstrated the feasibility to deliver monoclonal antibodies and peptides to the brain. Physiological transport mechanisms for some peptides (transferrin, insulin and others) are present at the barrier and were utilized to transport radiolabeled antibodies or Aβ peptide into brain. The existence of analogous uptake mechanisms in humans is known. That opens up the future possibility to quickly adapt an imaging method to clinical use once initial validation in a suitable animal model, like aged primates, was performed.

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  1. Institute of Pharmacology and Toxicology, Philipps University, Marburg, Germany

    Ulrich Bickel

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  1. Departments of Neurology and Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Marcel M. Verbeek

  2. Department of Pathology, University Medical Center St. Radboud, Nijmegen, The Netherlands

    Robert M. W. de Waal

  3. UCLA Medical Center, Los Angeles, CA, USA

    Harry V. Vinters

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Bickel, U. (2000). Diagnosis of CAA during Life. In: Verbeek, M.M., de Waal, R.M.W., Vinters, H.V. (eds) Cerebral Amyloid Angiopathy in Alzheimer’s Disease and Related Disorders. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1007-7_2

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